Enterococci are leading causes of nosocomial infection. Accumulating evidence indicates that multiple antibiotic resistant Enterococcal strains in the hospital environment colonize the GI tracts of patients within hours or days of admission. From the patient's own GI tract, the organisms are well positioned to colonize surgical sites, catheterized bladders, or invade the bloodstream from breaches in the integrity of the colon. Currently, little is known about the allogenic or autogenic factors that lead to GI tract colonization by these multiple resistant strains, and it is not known whether this colonization is competitive or non-competitive with indigenous commensal Enterococcal strains. We recently characterized a pathogenicity island that encodes precisely the types of traits that would be expected to alter the Enterococcal colonization pattern, including PTS uptake systems for metabolism of new carbohydrates, new surface adhesions, and a bile acid hydrolase that may render previously uninhabitable locations within the GI tract amenable to colonization by pathogenic Enterococcal lineages. The main barriers to progress in this area are the complexity of the GI tract flora compounded by patient-to-patient variability. To begin examining the first principles that dictate relationships between Enterococci and other organisms in the GI tract consortium, the occurrence of Enterococci within a simple in vitro model of the human GI tract consortium will be characterized. The GI tract consortium model will be established, and it will be determined whether Enterococcus faecalis and E. faecium exhibit colonization preferences for particular niches within the model, and whether they home to the same niche. It will further be determined whether commensal and pathogenic lineages of E. faecalis and E. faecium partition to the same location within the model. Organisms found to share the same niche as clinical isolates, and potentially contributing to a symbiotic relationship will be identified and tested, as will organisms occurring in sites from which Enterococci are excluded. Finally, the effect of antibiotics in shifting the colonization pattern of resistant clinical isolates in this in vitro model will be characterized. Based on these results, well-grounded specific questions can be postulated and tested subsequently to verify their importance in vivo, ultimately leading to the design of agents to prevent colonization by antibiotic resistant strains. [unreadable] [unreadable]